Clinical Evidence Concise

A Publication of BMJ Publishing Group

Autism

JEREMY PARR, University of Oxford Departments of Paediatrics and Child Psychiatry, Oxford, United Kingdom

Am Fam Physician. 2008 Sep 15;78(6):758-760.

Autism is one of a group of pervasive developmental disorders, and is characterized by qualitative impairments in communication and social interaction, and by repetitive and stereotyped behaviors and interests.

Abnormal development is present before three years of age. One fourth of affected children show developmental regression, with loss of previously acquired skills.

One third of children with autism have epilepsy, and three fourths have mental retardation. Only 15 percent of adults with autism lead independent lives.

Twin and family studies suggest that most cases of autism occur because of a combination of genetic factors. Autism is not caused by perinatal factors or by the measles, mumps, and rubella vaccine.

It may be difficult to apply research results in practice because improvements in outcomes studied in randomized controlled trials (RCTs) using standardized assessment tools may not correlate with improvements in function in a particular child with autism.

Some interventions are administered by (or in conjunction with) parents and may be carried out in the home. Consideration of direct financial costs, indirect costs (through possible lost earnings), and the impact on relationships within the family (siblings or spouse) must be balanced against likely and possible improvements in outcome for the child with autism.

There is a lack of good-quality evidence on the effectiveness of early multidisciplinary intervention programs or of other treatments for children with autism.

There is consensus, supported by a small RCT, that applied behavioral analysis is likely to be beneficial in children with autism.

Attendance at a More Than Words training course for parents may improve communication between parents and children, as may participation in Child's Talk.

There is consensus that the Autism Pre-school Programme and TEACCH (Treatment and Education of Autistic and related Communication-handicapped CHildren) may be effective, although we found no RCTs or cohort studies evaluating these interventions.

We do not know whether early intervention using the Early Bird Programme, the Portage scheme, relationship development intervention, Social Stories, or Son-Rise are beneficial in children with autism.

Methylphenidate may reduce hyperactivity in children with autism.

Methylphenidate may increase social withdrawal and irritability. Monitoring of growth and blood pressure is required.

Risperidone may improve behavior in children with autism compared with placebo, but its use is limited by adverse effects, such as weight gain, drowsiness, and tremors.

There is consensus that selective serotonin reuptake inhibitors (SSRIs) improve symptoms in children with autism, although we found no RCTs. The adverse effects of SSRIs, including possible increases in agitation, hostility, and suicidal ideation, are well documented.

We do not know whether auditory integration training, sensory integration training, chelation, a gluten-and casein-free diet, digestive enzymes, omega-3 fatty acids (fish oil), secretin, vitamin A, vitamin B6 (pyridoxine) plus magnesium, or vitamin C are beneficial for treating children with autism, because we found few studies on these interventions.

*—In the absence of robust evidence from randomized controlled trials in children with autism, categorization is based on observational evidence and strong consensus belief.

Definition

Autism is one of the pervasive developmental disorders, a group of conditions that also includes Asperger syndrome, pervasive developmental disorder not otherwise specified, Rett syndrome, and childhood disintegrative disorder. Collectively, autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified are often referred to as autistic spectrum disorders. However, Rett syndrome and childhood disintegrative disorder fall outside the autistic spectrum.

Autism is characterized by qualitative impairments in communication and social interaction and by restricted, repetitive, and stereotyped patterns of behaviors and interests. Abnormal development is present before three years of age. The clinical features required for a diagnosis of autism to be made are set out in the International Classification of Diseases, 10th ed., and Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Persons with autism have a history of language delay (single word or phrase speech delay), and one fourth lose previously acquired skills (regression), most commonly in the second year of life. One third of persons with autism develop epilepsy, and three fourths have mental retardation. Males are affected more commonly than females (3.5:1 to 4.0:1 male-to-female ratio). The findings of this review apply to children and adolescents with autism, and results may not be generalizable to children with other autistic spectrum disorders.

Diagnosis: The generally accepted assessment tools for autism are the Autism Diagnostic Interview-Revised (a semistructured, interviewer-based assessment administered to primary caregivers of persons with autism) and the Autism Diagnostic Observational Schedule (a semistructured assessment administered to persons with autism themselves). Although these assessment tools are informative for the physician, autism is a clinical diagnosis.

Incidence and Prevalence

The detected prevalence of autism has increased in recent years, and a high-quality study from the United Kingdom found 40 per 10,000 children to have childhood autism. The prevalence of autism in studies published between 1977 and 1991 was 4.4 per 10,000, whereas the prevalence was 12.7 per 10,000 in studies between 1992 and 2001. When considering all autism spectrum disorders, findings suggest the prevalence rises to 120 per 10,000; many of these persons have pervasive developmental disorder not otherwise specified.

Etiology and Risk Factors

Evidence from twin and family studies suggests that most cases of autism arise because of a combination of genetic factors. Family studies indicate that the rate of autism in the siblings of persons with autism is about 2.2 percent, and the sibling recurrence rate for all pervasive developmental disorders is 5 to 6 percent—significantly greater than that of the general population. Monozygotic twin studies show 60 to 91 percent concordance for autism; therefore, it is likely that most cases arise on the basis of multiple susceptibility genes, with influence from environmental or other factors. A minority of cases of autism can be attributed to genetic disorders, including chromosomal abnormalities, fragile X syndrome, tuberous sclerosis, neurofibromatosis type 1, and a variety of other medical conditions. Although perinatal factors have been implicated, it is unlikely that they have a causal role. Evidence suggests that autism is not caused by the measles, mumps, and rubella vaccine or by thimerosal (mercury) in vaccines. There is strong evidence supporting a neurobiological basis of autism.

Ongoing research into the relationship among neurophysiology, neuroanatomy, neurochemistry, and genetic factors is likely to increase our understanding, and it represents the best chance of unraveling the complex etiology of autistic spectrum disorders. The presence of phenotypic and genetic heterogeneity may have significant implications for studies of interventions and treatments for autism because effectiveness may vary with phenotype.

Prognosis

Autism is a lifelong condition with a highly variable clinical course throughout childhood and adolescence. Many adults with autism require full-time care. About 15 percent of adults with autism live independent lives, whereas 15 to 20 percent live alone with community support. Verbal and overall cognitive capacities seem to be the most important predictors of an ability to live independently as an adult.

This is one in a series of chapters excerpted from the Clinical Evidence Handbook, published by the BMJ Publishing Group, London, U.K. The medical information contained herein is the most accurate available at the date of publication. More updated and comprehensive information on this topic may be available in future print editions of the Clinical Evidence Handbook, as well as online at http://www.clinicalevidence.bmj.com (subscription required). Those who receive a complimentary print copy of the Clinical Evidence Handbook from United Health Foundation can gain complimentary online access by registering on the Web site using the ISBN number of their book.